Perfusion Estimation For Optimal Treatment Strategy in Chronic Coronary Syndrome

NCT ID: NCT05865600

Last Updated: 2025-12-10

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 570 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-05-23
• Study Completion Date: 2027-09-01

Brief Summary

We will establish a cohort of 570 symptomatic chronic coronary syndrome patients undergoing 15O-water PET and assess their symptoms through repeated questionnaires. Two hundred patients with abnormal perfusion will be randomized to immediate or delayed referral to invasive coronary angiography with concomitant optimization of guideline-directed medical therapy with repeated 15O-water PET and questionnaires at 3 and 6 months. The primary objective is to compare the potential benefit of early invasive coronary angiography (ICA) versus guideline directed medical therapy (GDMT) on symptomatic relief defined as freedom of angina after 3 months following a positive [15O]H2O cardiac PET/CT in patients with symptomatic chronic coronary syndrome.

Detailed Description

BACKGROUND:

Ischemic heart disease (IHD) is highly prevalent in Western countries and an emerging disease in developing countries around the globe. While the Danish incidence rate of IHD for both females and males has been declining during the last 15 years, the prevalence has stabilized at 165,000 patients in 2018 due to enhanced survival.

Ischemic heart disease is caused by atherosclerotic plaque formation in the epicardial coronary arteries, abnormalities in the coronary microcirculation, spasms in the vessel wall, or a combination thereof. This may result in chest discomfort or dyspnoea leading to frequent primary care consultations and admissions on the suspicion of acute coronary syndrome. To emphasize the chronic nature of the disease, the European Society of Cardiology has replaced the previous nomenclature of stable coronary artery disease with chronic coronary syndrome (CCS) in their latest guidelines from 2019.

When cardiac imaging is used to diagnose and select treatment in patients with CCS, guidelines recommend non-invasive functional imaging modalities in patients with an intermediate or high clinical likelihood of IHD or in patients with prior revascularization. In patients with prior myocardial infarction or percutaneous coronary intervention, studies have found higher diagnostic accuracy of [15O]H2O cardiac PET/CT with measurement of absolute quantification of myocardial perfusion to diagnose obstructive coronary artery disease compared with single-photon emission computed tomography and magnetic resonance imaging. Current European guidelines recommend myocardial revascularization in addition to guideline-directed medical therapy (GDMT) in CCS patients with large areas of ischemia (≥ 10%) in the left ventricle to improve prognosis.

Since the publication of these guidelines, a large randomized trial of initial invasive versus conservative strategy in patients with moderate-severe ischemia on stress testing has been published with no observed prognostic benefit of an initial invasive strategy in these patients. However, patients assigned to an initial invasive strategy had a greater improvement in angina-related health status as compared with a conservative strategy, with larger differences observed in patients who were more symptomatic at baseline. The study is limited by the high use of stress ECG (25% of participants) which has a very low diagnostic power and the high proportion of asymptomatic participants at baseline (35%).

It is unknown whether the results of MPI with absolute quantification of myocardial perfusion can improve the selection of patients with an additional symptomatic benefit of an initial invasive strategy compared with GDMT.

METHODS:

Patients with symptomatic CCS referred for clinically indicated [15O]H2O cardiac PET/CT will be included in a prospective cohort and assessed with questionnaires at baseline, 3, 6, 12, 60, and 120 months. Clinical outcomes will be assessed through national registries.

Patients with abnormal perfusion and a clinical indication for ICA will undergo coronary CT angiography and a six-minute walking test. Hereafter, they will be randomized 1:1 to immediate referral to ICA or 3 months delayed referral to ICA. Both groups will undergo optimization of GDMT with consultations every two weeks.

At 3 and 6 months, both groups will undergo repeated questionnaires, [15O]H2O cardiac PET/CT and a six-minute walking test.

Enrollment in the cohort study and randomized trial will continue until 200 randomized patients have reached the 3 months assessment.

Conditions

Chronic Coronary Syndrome; Myocardial Ischemia; Stable Angina; Coronary Artery Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

Cohort study

All patients with symptomatic chronic coronary syndrome undergoing clinically referred \[15O\]H2O cardiac PET/CT will be included in a prospective cohort with repeated symptom questionnaires and outcomes registered in national registries. A total of 570 patients are expected to be included in order to have 200 randomized patients reaching the 3-month assessment

Group Type: OTHER

Standard of care

Intervention Type: OTHER

Standard of care

Immediate referral to invasive coronary angiography

Patients with abnormal perfusion on \[15O\]H2O cardiac PET/CT and clinical indication for invasive coronary angiography randomized to immediate referral for invasive coronary angiography with concomitant optimization of guideline-directed medical therapy. Enrollment will continue until a total of 200 randomized patients reach the 3-month assessment.

Group Type: EXPERIMENTAL

Optimization of guideline-directed medical therapy

Intervention Type: OTHER

Consultation every second week with optimization of guideline-directed medical therapy according to 2019 ESC guidelines on chronic coronary syndrome. Focus will be on risk-factor modification and anti-anginal medication with the treatment aim to achieve freedom from angina and dyspnea with a heart rate at rest ≤ 60 beats/min and systolic blood pressure \> 100 mmHg.

Immediate referral for invasive coronary angiography

Intervention Type: DIAGNOSTIC_TEST

Immediate referral for invasive coronary angiography

Delayed referral to invasive coronary angiography

Patients with abnormal perfusion on \[15O\]H2O cardiac PET/CT and clinical indication for invasive coronary angiography randomized to 3-months delayed referral for invasive coronary angiography with concomitant optimization of guideline-directed medical therapy. Enrollment will continue until a total of 200 randomized patients reach the 3-month assessment.

Group Type: EXPERIMENTAL

Optimization of guideline-directed medical therapy

Intervention Type: OTHER

Consultation every second week with optimization of guideline-directed medical therapy according to 2019 ESC guidelines on chronic coronary syndrome. Focus will be on risk-factor modification and anti-anginal medication with the treatment aim to achieve freedom from angina and dyspnea with a heart rate at rest ≤ 60 beats/min and systolic blood pressure \> 100 mmHg.

3-months delayed referral for invasive coronary angiography

Intervention Type: DIAGNOSTIC_TEST

3-months delayed referral for invasive coronary angiography

Interventions

Optimization of guideline-directed medical therapy

Consultation every second week with optimization of guideline-directed medical therapy according to 2019 ESC guidelines on chronic coronary syndrome. Focus will be on risk-factor modification and anti-anginal medication with the treatment aim to achieve freedom from angina and dyspnea with a heart rate at rest ≤ 60 beats/min and systolic blood pressure \> 100 mmHg.

Intervention Type: OTHER

Immediate referral for invasive coronary angiography

Immediate referral for invasive coronary angiography

Intervention Type: DIAGNOSTIC_TEST

3-months delayed referral for invasive coronary angiography

3-months delayed referral for invasive coronary angiography

Intervention Type: DIAGNOSTIC_TEST

Standard of care

Standard of care

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

1. Age > 18 years

2. Willing to participate and able to understand, read and sign the informed consent document before the planned procedure

3. Known ischemic heart disease defined as one of the following

1. Previous myocardial infarction, percutaneous coronary intervention or coronary artery bypass grafting

2. Previous coronary computed tomography angiography or invasive coronary angiography documenting atherosclerosis.

4. Undergoing clinically indicated [15O]H2O cardiac PET/CT due to chest discomfort or dyspnea as angina equivalent

5. Initial [15O]H2O cardiac PET/CT with abnormal perfusion defined as all of the following

1. Hyperemic myocardial blood flow (hMBF) ≤2.3 mL/min/g in at least two adjacent myocardial segments

2. Relative hMBF ≤ 65% in at least two adjacent segments as compared with the mean hMBF of the two adjacent segments with the highest mean hMBF

3. Tissue perfusion defect extent ≥ 5% based on indices of relative hypoperfusion

6. Clinical indication for invasive coronary angiography decided at a multidisciplinary conference between consultants in nuclear medicine and cardiology

Exclusion Criteria

1. Ongoing acute coronary syndrome or acute coronary syndrome within 30 days

2. Contraindications for adenosine

1. Severe asthma

2. Advanced atrioventricular block without pacemaker

3. Severe aortic stenosis

3. Patients not able to breath hold (severe COPD/asthma)

4. Pregnant women, including women who are potentially pregnant or lactating

5. Allergy to iomeron

6. Life expectancy of less than 2 years

7. Severe valvular disease

8. Reduced kidney function with an estimated glomerular filtrations rate <40 ml/min

9. Inability to consent

10. Unprotected left main coronary artery stenosis on coronary CT angiography

11. Very large perfusion defect on initial [15O]H2O cardiac PET/CT indicating left main coronary artery stenosis or balanced ischemia defined as tissue perfusion defect extent based on indices of absolute hMBF ≥ 20% in two or more myocardial territories supplied by coronary arteries with an Agatston calcium score ≥ 300

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Gødstrup Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Morten Böttcher, Prof

Role: PRINCIPAL_INVESTIGATOR

University Clinic for Cardiovascular Research, Dept. of Cardiology, Gødstrup Hospital

Locations

Gødstrup Hospital

Herning, Central Jutland, Denmark

Site Status: RECRUITING

Countries

Denmark

Central Contacts

Jacob H Søby, MD

Role: CONTACT

jasoeb@rm.dk

61659131 ext. 0045

Facility Contacts

Morten Böttcher, Prof

Role: primary

morboett@rm.dk

25775134 ext. 0045

Jacob H Søby, MD

Role: backup

jasoeb@rm.dk

61659131 ext. 0045

Other Identifiers

1-10-72-185-22

Identifier Type: -

Identifier Source: org_study_id